Human hookworm disease, a clinical condition caused by Ancylostoma duodenale or Necator americanus infection, affects an estimated 950 million people in the developing world (Banwell, J. G., and G. A. Schad. 1978. Clinics in Gastroenterology 7:129). The adult parasites, using their buccal cavities and hooklike teeth, attach themselves to villi in the small intestine. Each worm can then extract up to 0.20 ml of blood per day causing intestinal blood loss and ultimately iron-deficiency anemia and hypoalbuminemia in the host. (Roche, M., and M. Layrisse. 1966. Am. J. Trop. Med. Hyg. 15:1031; Miller, T. A. 1968. Roy. Soc. Trop. Med. Hyg. 62:473).
Although it is possible to cure hookworm infection by known anthelminic agents, widespread infestation of the human and canine population persists. Of the approximately 50 million dogs currently living in the United States a large percentage have hookworm infection. An effective vaccine would eliminate this persistent parasite in canine carriers and in human carriers as well.
Gamma-irradiated larvae of Ancylostoma caninum have been used as a vaccine against canine hookworm. Although the vaccine was produced and marketed, it did not prove to be commercially successful due in part to a short shelf-life (Miller T., (1971) Ad. Parasitology 9:153). Accordingly, a safe, effective and commercially feasible vaccine for prevention and treatment of hookworm infection has been sought.
An interesting and provocative aspect of infection by blood sucking nematodes is the fact that the parasites are able to prevent blood coagulation while feeding (Loeb, L. and M. S. Fleisher. 1910. J. Infec. Dis. 7:625). To date the biochemical mechanism which allows hookworms to prevent blood coagulation while feeding remains unexplained. Previous studies have shown that extracts of the dog hookworm Ancylostoma caninum can prolong prothrombin time, with variable effects on partial thromboplastin time, and interfere with collagen or ADP-induced platelet aggregation, as well as inhibit the action of factor Xa (Spellman, G.G., and H. L. Nossel. 1971. Am. J. Physiol. 220:922). .
A proteolytic enzyme with anticlotting properties has recently been found in the giant leech Haementeria ghilianii (Budzynski, A. Z., Olexa, S. A., Brizuela, B. S., Sawyer, R. T., and G. S. Stent. 1981. Proc. Soc. Exp. Biol. Med. 168:266). A similar proteolytic anticoagulant has been sought in the Ancylostoma hookworms and other blood-sucking nematodes.